Phase I Study of Ceralasertib (AZD6738), a Novel DNA Damage Repair Agent, in Combination with Weekly Paclitaxel in Refractory Cancer.

ABSTRACT:

Purpose

Ceralasertib is a potent and selective oral inhibitor of the serine/threonine protein kinase ataxia telangiectasia and Rad3-related (ATR) protein.

Patients and methods

Eligible patients with solid tumors, enriched for melanoma, received ceralasertib in combination with a fixed dose of paclitaxel (80 mg/m² on D1, D8, D15) in 28-day cycles. The dose of ceralasertib was escalated to reach an MTD in a rolling 6 design. The starting dose of ceralasertib was 40 mg QD. Fifty-seven patients (33 patients with melanoma who failed prior PD1/L1 treatment) were enrolled in 7 dose cohorts ranging from 40 mg QD to 240 mg BD plus weekly paclitaxel.

Results

The RP2D was established as ceralasertib 240 mg BD days 1-14 plus paclitaxel 80 mg/m² on D1, D8, D1

SUBMITTER: Kim ST 

PROVIDER: S-EPMC8974415 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature